This second revision of 5 year clinical scientist training proposal describes the program to provide new scientific knowledge and facilitate the transition to an independent cardiovascular research career as a Molecular Cardiologist. The applicant has completed clinical training and is board certified in both Internal Medicine and Cardiology. The applicant has engaged in basic science and clinical physiology research and will utilize the expertise and resources within multiple departments at the University of Colorado to gain proficiency in a new area of scientific evaluation. The training program will focus on the biochemistry and molecular biology of sex differences in cardiac disease. Dr. Leslie Leinwand will mentor the principal investigator's scientific development. She is recognized as a leader in the molecular biology of cardiomyopathies. The program has enlisted several expert clinical molecular cardiologists and a molecular endocrinologist as co-Sponsors. The advisory committee is composed of faculty who are nationally and internationally renowned in their particular field. Over the past several decades a sex-dependent difference in cardiac phenotype has been described in clinical hypertrophic disease, however, the mechanisms behind this difference remain elusive. Recent work by the applicant has discovered sex dependent differences in cardiac functional phenotype in an animal model of hypertrophic cardiomyopathy which can be altered by dietary modification. This model will serve to begin the dissection of molecular and cellular mechanisms behind this disease. The specific aims propose to identify the molecular pathways involved in this sex dependent difference and will evaluate sex hormones and diet as interventions which modify the pathophysiologic phenotype. The investigator proposes to identify the mechanism by which altering the diet prevents the development of a sex-dependent dilated cardiomyopathic phenotype. In addition, the investigator proposes to determine the contribution of sex hormones to the sex-dependent differences in hypertrophic cardiac disease. The Department of Cardiology at the University of Colorado provides the ideal location to train basic research clinician-scientists through the integration of interdepartmental and intercampus expertise. The department's flexibility provides investigators with the support necessary to utilize all available resources to tailor the research program toward a unique focus necessary to launch an independent research career. (End of Abstract)